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Modulation of pp60 v‐src and pp60 c‐src expression in rous sarcoma virus—transformed hamster fibroblasts transfected with activated N‐ ras
Author(s) -
Topol Lilia Z.,
Gutierrez Maria L.,
Blair Donald G.,
Kisseljova Natalya P.,
Musatkina Elena A.,
Shtutman Michael S.,
Zakamaldina Tatyana Z.,
Tatosyan Alexander G.,
Deichman Galina I.
Publication year - 1993
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940080307
Subject(s) - rous sarcoma virus , biology , proto oncogene tyrosine protein kinase src , microbiology and biotechnology , transfection , hamster , cell culture , kinase , virus , virology , genetics
Three phenotypically different hamster cell lines transformed with Rous sarcoma virus (RSV) were transfected with plasmid DNA containing an activated N‐ ras oncogene, and nine clones expressing various levels of p21 N‐ras were characterized. We examined the effects of p21 N‐ras on expression and kinase activity of resident src proteins by using a variety of assays that allowed us to discriminate between viral and cellular src proteins. In eight clones with a 10‐ to 20‐fold increase in p21 N‐ras levels relative to the endogenous protein, we observed a marked reduction in the synthesis and kinase activity of p60 v‐src . This decrease correlated with transcriptional downregulation of RSV genomic and v‐ src subgenomic mRNAs. In the same cells, we found a concomitant accumulation of p60 c‐src and, accordingly, an increase in its protein kinase activity without an apparent increase in c‐ src mRNA levels. Therefore, modulation of viral and cellular src proteins in cells overexpressing p21 N‐ras appeared to result from two distinct effects: a downregulation of long terminal repeat—driven transcription and a more complex interaction with cellular effectors that control the stability of p60 c‐src . Such modulation also seemed to depend on the levels of p21 N‐ras and, possibly, on host‐cell factors, since it was not observed in the third cell line, in which the relative increase in p21 N‐ras was only 2.5‐fold to fivefold.